Greater knee laxity has been identified as a predictor of ACL injury risk in females, and there is now sufficient evidence that sex hormones mediate cyclic changes in knee laxity across the menstrual cycle and in large part account for greater knee laxity in females compared to males. Our objective for this proposal is to determine the consequence of both greater absolute baseline anterior knee laxity (ABSAKi.) and cyclic increases in anterior knee laxity (CYCAKi.) on knee joint neuromechanics during functional activities. Our approach will be to recruit males and females with a broad range of baseline knee laxity values, then track females across their menstrual cycle to identify the specific days in their early follicular and luteal phases when knee laxity values are at their minimum and maximum respectively. We will then measure males and females on weight bearing knee joint neuromechanics at these specified time points to examine the independent and combined effects of sex, absolute baseline knee laxity and cyclic increases in knee laxity on knee joint neuromechanics. Our central hypothesises that greater absolute baseline and greater cyclic increases in knee laxity will independently and in combination predict greater anterior tibial translation during the transition from non-weight bearing to weight bearing, and greater "functional valgus collapse" of the knee during a single leg weight bearing perturbation. Our rationale for examining the effects of both greater absolute baseline and cyclic increases in knee laxity on weight bearing knee joint neuromechanics is that the successful completion of this work will advance our understanding of the factors contributing to "at risk" joint positions that are known to strain and injure the ACL. Because we expect that cyclic increases in knee laxity will be a significant predictor of at risk knee joint neuromechanics, we also plan to develop a predictive algorithm that will better enable clinicians and researchers in future prospective studies to reliably identify female hormone responders (those who experience cyclic increases in knee laxity > 3mm) based on several key hormone measures. ACL injury can profoundly impact on health and physical activity, both immediately following injury and reconstructive surgery, and later in life as a consequence of the early onset of osteoarthritis. These complications are of greatest concern in young active females, who are at a 2 to 9 times greater risk of suffering ACL injury compared to equivalently trained males. Advancing our knowledge of the underlying pathophysiological mechanism(s) of ACL injuries will further the development of optimal prevention, rehabilitation and training strategies to reduce the risk of sport-related injury, thereby enhancing the beneficial effects of physical activity on women's health for all ages. [unreadable] [unreadable]